The major objective is to investigate the relationship between: 1) the dietary content of either high saturated fat, high unsaturated fat, or low fat; 2) the stress caused by a lack of antioxidant content in the diet; and 3) the tumorigenic action of two different carcinogens. Diets with high or low fat content will be used, in which antioxidant will either be present or absent. Although high fat diets have been demonstrated to enhance tumorigenesis by certain carcinogens, and diets supplemented with antioxidants have been reported to depress carcinogenesis by such compounds, the relationship between these phenomena has not been studied. It appears well worth investigating this area since there is ample information sugesting that peroxidative reactions of lipid may be involved in the promotion of tumor formation initiated by carcinogens. The protective action of antioxidants against a number of carcinogens may be due to their capacity to inhibit lipid peroxidation in which case an antagonistic effect should be observed in animals fed diets high in polyunsaturated fat, i.e. antioxidant supplementation may be less effective in this group than in the other dietary groups in depressing tumor incidence. The animals fed the polyunsaturated fat diet which is deficient in antioxidant might be expected to develop a greater incidence of tumors at an earier time than animals fed antioxidant-deficient diets containing saturated fat or very little fat. On the other hand, the protective action of dietary antioxidants against carcinogenesis may be related to possible induction of certain drug-metabolizing enzymes which could then influence metabolism of carcinogens. The project is designed to obtain information which will indicate whether or not either or both of these two mechanisms may be operative.